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1. (WO2015157409) MITOCHONDRIA-TARGETING PLATINUM(IV) PRODRUG
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

is claimed is:

A compound of comprising one or more mitochondria targeting moieties conjugated to a Pt(IV) prodrug, wherein reduction of the Pt(IV) prodrug to Pt(II) releases the one or more mitochondria-targeting moieties and results in a Pt(II) therapeutic agent.

2. A compound according to claim 1, wherein the Pt(IV) prodrug comprises two mitochondria targeting moieties.

A compound of Formula I:


(I), wherein

each Q1, Q2, Q3, and Q4 independently represents a neutral or negatively charged ligand, with the proviso that at most two of Q1, Q2, Q3, and Q4 can represent negatively charged ligands, and wherein two or more of Q\ Q2> Q3> and Q4 can optionally be joined to form one or more five- or six-membered platinocyclic rings;


R2 is OH or -(L2)x-(R4)y;

R3 is a mitochondria targeting moiety;

R4 is a conjugated cyclooxygenase inhibitor, a targeting moiety, a fluorophore, a glycolysis inhibitor, or a mitochondria acting therapeutic agent,

wherein if R4 is a mitochondria targeting moiety, R3 and R4 are the same or different;

L1 is a linker;

L2 is a linker, wherein L1 and L2, if both are present, are the same or different; m and x are independently zero or one; and

n and y are independently an integer greater than or equal to 1.

A compound according to claim 3, wherein when m = 0, n =1 and when y = l .

5. A compound according to claim 3 or claim 4, wherein one or two of Q1, Q2, Q3, and Q4 are negatively charged ligands.

6. A compound according to claim 5, wherein two of Q1, Q2, Q3, and Q4 are negatively charged ligands.

7. A compound according to claim 5 or claim 6, wherein each of Q1, Q2, Q3, and Q4 that is a negatively charged ligand is selected from the group consisting of a halide, an alkoxide, an aryloxide, a carboxylate, and a sulfate.

8 A compound according to claim 7, wherein each of Q1, Q2, Q3, and Q4 that is a negatively charged ligand is a halide.

9. A compound according to claim 7, wherein each of Q1, Q2, Q3, and Q4 that is a negatively charged ligand is a chloride.

10. A compound according to any one of claims 3-9, wherein one or two of Q1, Q2, Q3, and Q4 are neutral ligands.

1 1. A compound according to claim 10, wherein each of Q1, Q2, Q3, and Q4 that is a neutral ligand is independently selected from the group consisting of R3N, wherein each R individually represents H or an organic group, wherein two or more R groups can optionally be joined to form one or more rings; and nitrogen-containing heteroaromatics.

12. A compound according to claim 11, wherein each of Q1, Q2, Q3, and Q4 that is a neutral ligand is independently R3N.

13. A compound according to claim 10, wherein each of Q1, Q2, Q3, and Q4 that is a neutral ligand is NH3.

14. A compound according to any one of claims 3-13, wherein R4 is a mitochondria targeting moiety.

A compound of Formula IV:

(IV), wherein


R2 is OH or -(L2)x-(R4)y;

R3 is a mitochondria targeting moiety;

R4 is a conjugated cyclooxygenase inhibitor, a targeting moiety, a fluorophore, a glycolysis inhibitor, or a mitochondria acting therapeutic agent, wherein if R4 is a mitochondria targeting moiety, R3 and R4 are the same or different;

L1 is a linker;

L2 is a linker, wherein L1 and L2, if both are present, are the same or different; m and x are independently zero or one;

n and y are independently an integer greater than or equal to 1 ;

each Y independently represents a negatively charged ligand, wherein both Y ligands may optionally be joined to form a five- or six-membered platinocyclic ring; and

each L independently represents a neutral ligand, wherein both L ligands may optionally be joined to form a five- or six-membered platinocyclic ring.

16. A compound of Formula V, VI, or VII:


wherein one or both of R1 and R2 comprise a mitochontria targeting moieties.

A compound according to claim 16, wherein the compound is a compound of Formula (V):


18. A compound according to claim 16 or claim 17, wherein both R1 and R2 comprise mitochontria targeting moieties.

A compound according to claim 16 or claim 17, wherein one of R1 and R2 comprises a mitochondria targeting moiety and the other of R1 and R2 comprises a cyclooxygenase inhibitor, a targeting moiety other than a mitochondria targeting mooiety, a fluorophore, a glycolysis inhibitor, or a mitochondria acting therapeutic agent, or is OH.

A compound according to any one of the preceding claims, wherein at least mitochondria targeting moiety comprises triphenyl phosophonium (TPP), a rhodamine cation, or a Szeto-Shiller peptide.

21. A compound according to any one of the preceding claims, wherein at least one mitochondria targeting moiety comprises TPP.

A Platin-M compound:


23. A nanoparticle comprising a compound according to any one of the preceding claims.

24. A nanoparticle according to claim 23, wherein the nanoparticle further comprises a mitochondria targeting moiety.

25. Use of a compound according to any one of claims 1-22 or a nanoparticle according to claim 23 or claim 24 in treating cancer in a subject in need thereof.

26. A method comprising administering a compound according to any one of claims 1-22 or nanoparticle according to claim 23 or claim 24 to a subject.

27. A method for treating cancer in a subject in need thereof, comprising administering an effective amount of a compound according to any one of claims 1-22 or a nanoparticle according to claim 23 or claim 24 to the subject.

28. A method for treating a disease in a brain of a subject, comprising administering a compound according to any one of claims 1-22 or a nanoparticle according to claim 23 or claim 24 to the subject.

29. A method according to claim 28, wherein the compound or nanoparticle is administered systemically.

30. A method for treating a disease of the mitochondria in a subject, the method comprising administering a compound according to any one of claims 1-22 or a nanoparticle according to claim 23 or claim 24 to the subject.